Integrative Analysis of DNA Methylation Data and Transcriptome Data Identified a DNA Methylation-Dysregulated Four-LncRNA Signature for Predicting Prognosis in Head and Neck Squamous Cell Carcinoma

Qiuxu Wang; Weiwei Yang; Wei Peng; Xuemei Qian; Minghui Zhang; Tianzhen Wang

doi:10.3389/fcell.2021.666349

Integrative Analysis of DNA Methylation Data and Transcriptome Data Identified a DNA Methylation-Dysregulated Four-LncRNA Signature for Predicting Prognosis in Head and Neck Squamous Cell Carcinoma

Front Cell Dev Biol. 2021 Apr 1:9:666349. doi: 10.3389/fcell.2021.666349. eCollection 2021.

Authors

Qiuxu Wang^{1

2}, Weiwei Yang³, Wei Peng², Xuemei Qian³, Minghui Zhang⁴, Tianzhen Wang³

Affiliations

¹ Department of Stomatology, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen Second People's Hospital, Shenzhen, China.
² Department of Stomatology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
³ Department of Pathology, Harbin Medical University, Harbin, China.
⁴ Department of Oncology, Chifeng City Hospital, Chifeng, China.

Abstract

Increasing evidence has demonstrated the crosstalk between DNA epigenetic alterations and aberrant expression of long non-coding RNAs (lncRNAs) during carcinogenesis. However, epigenetically dysregulated lncRNAs and their functional and clinical roles in Head and Neck Squamous Cell Carcinoma (HNSCC) are still not explored. In this study, we performed an integrative analysis of DNA methylation data and transcriptome data and identified a DNA methylation-dysregulated four-lncRNA signature (DNAMeFourLncSig) from 596 DNA methylation-dysregulated lncRNAs using a machine-learning-based feature selection method, which classified the patients of the discovery cohort into two risk groups with significantly different survival including overall survival, disease-specific survival, and progression-free survival. Then the DNAMeFourLncSig was implemented to another two HNSCC patient cohorts and showed similar prognostic values in both. Results from multivariable Cox regression analysis revealed that the DNAMeFourLncSig might be an independent prognostic factor. Furthermore, the DNAMeFourLncSig was substantially correlated with the complete response rate of chemotherapy and may predict chemotherapy response. Functional in silico analysis found that DNAMeFourLncSig-related mRNAs were mainly enriched in cell differentiation, tissue development and immune-related pathways. Overall, our study will improve our understanding of underlying transcriptional and epigenetic mechanisms in HNSCC carcinogenesis and provided a new potential biomarker for the prognosis of patients with HNSCC.

Keywords: DNA methylation; biomarker; head and neck squamous cell carcinoma; long-coding RNAs; signature.